[Federal Register: June 8, 2004 (Volume 69, Number 110)]
[Notices]               
[Page 32010-32011]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr08jn04-75]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 2002D-0237]

 
International Conference on Harmonisation; Evaluation of 
Stability Data; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a guidance entitled ``Q1E Evaluation of Stability 
Data.'' The guidance was prepared under the auspices of the 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use (ICH). This guidance is a 
supplement to an ICH guidance entitled ``Q1A(R2) Stability Testing of 
New Drug Substances and Products,'' which was revised from Q1A(R) and 
published in the Federal Register of November 21, 2003 (68 FR 65717). 
It is intended to provide guidance on how to use stability data, 
generated in accordance with the principles outlined in Q1A(R2), to 
propose a retest period for the drug substance and a shelf life for the 
drug product.

DATES: The guidance is effective June 8, 2004. Submit written or 
electronic comments at any time.

ADDRESSES: Submit written comments on the guidance to the Division of 
Dockets Management (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. Submit electronic comments 
to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments. Submit written requests for 

single copies of the guidance to the Division of Drug Information (HFD-
240), Center for Drug Evaluation and Research, Food and Drug 
Administration, 5600 Fishers Lane, Rockville, MD 20857, or the Office 
of Communication, Training, and Manufacturers Assistance (HFM-40), 
Center for Biologics Evaluation and Research, Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1448, 301-827-
3844. Send two self-addressed adhesive labels to assist the office in 
processing your requests. Requests and comments should be identified 
with the docket number found in brackets in the heading of this 
document. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance.

FOR FURTHER INFORMATION CONTACT:
    Regarding the guidance: Chi-wan Chen, Center for Drug Evaluation 
and Research (HFD-830), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-827-2001; or Andrew Shrake, Center for 
Biologics Evaluation and Research (HFM-345), Food and Drug 
Administration, 1401 Rockville Pike, Rockville, MD 20852-1148, 301-402-
4635.
    Regarding the ICH: Janet Showalter, Office of International 
Programs (HFG-1), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-827-0864.

SUPPLEMENTARY INFORMATION:

I. Background

    In recent years, many important initiatives have been undertaken by 
regulatory authorities and industry associations to promote 
international harmonization of regulatory requirements. FDA has 
participated in many meetings designed to enhance harmonization and is 
committed to seeking scientifically based harmonized technical 
procedures for pharmaceutical development. One of the goals of 
harmonization is to identify and then reduce differences in technical 
requirements for drug development among regulatory agencies.
    ICH was organized to provide an opportunity for tripartite 
harmonization initiatives to be developed with input from both 
regulatory and industry representatives. FDA also seeks input from 
consumer representatives and others. ICH is concerned with 
harmonization of technical requirements for the registration of

[[Page 32011]]

pharmaceutical products among three regions: The European Union, Japan, 
and the United States. The six ICH sponsors are the European 
Commission, the European Federation of Pharmaceutical Industries 
Associations, the Japanese Ministry of Health, Labour, and Welfare, the 
Japanese Pharmaceutical Manufacturers Association, the Centers for Drug 
Evaluation and Research and Biologics Evaluation and Research, FDA, and 
the Pharmaceutical Research and Manufacturers of America. The ICH 
Secretariat, which coordinates the preparation of documentation, is 
provided by the International Federation of Pharmaceutical 
Manufacturers Associations (IFPMA).
    The ICH Steering Committee includes representatives from each of 
the ICH sponsors and the IFPMA, as well as observers from the World 
Health Organization, Health Canada's Health Products and Food Branch, 
and the European Free Trade Area.
    In the Federal Register of June 14, 2002 (67 FR 40949), FDA 
published a draft tripartite guidance entitled ``Evaluation of 
Stability Data.'' The notice gave interested persons an opportunity to 
submit comments by August 1, 2002.
    After consideration of the comments received and revisions to the 
guidance, a final draft of the guidance was submitted to the ICH 
Steering Committee and endorsed by the three participating regulatory 
agencies in February 2003.
    This guidance complements an ICH guidance entitled ``Q1A(R2) 
Stability Testing of New Drug Substances and Products,'' which was 
revised from Q1A(R) and published in the Federal Register of November 
21, 2003. The guidance is intended to provide recommendations on how to 
use stability data, generated in accordance with the principles 
outlined in Q1A(R2), to propose a retest period for the drug substance 
and a shelf life for the drug product.
    The recommendations on the evaluation and statistical analysis of 
stability data provided in Q1A(R2) are brief in nature and limited in 
scope. Although Q1A(R2) states that regression analysis is an 
acceptable approach to analyzing quantitative stability data for retest 
period or shelf life estimation and recommends that a statistical test 
for batch poolability be performed using a level of significance of 
0.25, it includes few details. In addition, Q1A(R2) does not cover 
situations where multiple factors are involved in a full- or reduced-
design study. This guidance provides a clear explanation of the 
expectations when proposing a retest period or shelf life and storage 
conditions based on the evaluation of stability data for both 
quantitative and qualitative test attributes. It outlines 
recommendations for establishing a retest period or shelf life based on 
stability data from single or multifactor and full- or reduced-design 
studies. The guidance further describes when and how limited 
extrapolation can be undertaken to propose a retest period or shelf 
life beyond the observed range of data from the long-term storage 
condition.
    This guidance represents the agency's current thinking on this 
topic. It does not create or confer any rights for or on any person and 
does not operate to bind FDA or the public. An alternative approach may 
be used if such approach satisfies the requirements of the applicable 
statutes and regulations.

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments on the guidance. Submit 
a single copy of electronic comments or two paper copies of any mailed 
comments, except that individuals may submit one paper copy. Comments 
are to be identified with the docket number found in brackets in the 
heading of this document. The guidance and received comments may be 
seen in the Division of Dockets Management between 9 a.m. and 4 p.m., 
Monday through Friday.

III. Electronic Access

    Persons with access to the Internet may obtain the document at 
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm, http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm, or http://www.fda.gov/cber/publications.htm.


    Dated: May 29, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-12889 Filed 6-7-04; 8:45 am]

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